Sitagliptin and the Risk for Hypoglycaemia in Type 2 Diabetes Patients

DPP-4 Inhibition With Sitagliptin and the Risk for Hypoglycaemia in the Fasting State in Subjects With Type 2 Diabetes Treated to Fasting Plasma Glucose Targets With Insulin Glargine and Metformin

Sitagliptin, through its effects on sensitizing alpha-cell sensitivity to glucose, can initiate counter-regulatory glucagon responses at higher glycemic thresholds, thus reducing the number of clinically apparent hypoglycemic episodes, and/or ameliorating the severity of hypoglycemic episodes in the case that they should occur. The endpoints have defined such that consequences of this hypothesis can be measured.

Study Overview

• Status: Completed
• Conditions: Pharmacological Action
• Intervention / Treatment: Drug: Sitagliptin 100 mg; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Neuss, Germany
    • Profil Institut für Stoffwechselforschung GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subject with diabetes mellitus type 2.
• Age between 18 and 64 years, both inclusive.
• HbA1c <= 8.5%.
• Stable treatment with insulin glargine (any dose) and metformin (>= 1500 mg/day or at highest tolerated dose) for at least 3 months prior to inclusion into the trial with or without additional oral glucose-lowering agents (except thiazolidinediones).
• Considered generally healthy (apart from diabetes mellitus type 2 and associated conditions such as hypertension, hyperlipidaemia and hyperuricaemia) upon completion of medical history, physical examination, vital signs, ECG and analysis of laboratory safety variables, as judged by the Investigator.

Exclusion Criteria:

• Known or suspected hypersensitivity to sitagliptin or related products.
• More than one episode of severe hypoglycaemia with seizure, coma or requiring medical assistance of another person during the past 6 months or hypoglycaemic unawareness as judged by the Investigator.
• Current or previous treatment (less than 3 months prior to screening) with insulin products other than insulin glargine and/or with Glucagon-like peptide (GLP) 1 receptor agonists and/or with thiazolidinediones.
• Unwillingness to wash-off any oral glucose-lowering agents other than metformin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sitagliptin arm; Sitagliptin 100 mg	Drug: Sitagliptin 100 mg; The treatment consists of sitagliptin tablets (100 mg/day) for up to 24 weeks.
Placebo Comparator: Placebo arm; Placebo comparator	Drug: Placebo; The treatment consists of placebo tablets for up to 24 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Frequency of Hypoglycaemic Episodes With Sitagliptin vs Placebo Treatment.	The purpose of the trial was to test the influence of DPP-4 inhibition on the risk to develop hypoglycaemia. Chemical hypoglycaemic episodes (characterised by a plasma glucose nadir ≤70 mg/dL) occurring during the in-house periods of the subjects were compared.	during the two in-house periods (54 hs each) after treatment with sitagliptin or placebo for up to 24 weeks

Collaborators and Investigators

• Sponsor: Profil Institut für Stoffwechselforschung GmbH
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Christoph Kapitza, MD, Profil GmbH

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2018
• Primary Completion (Actual): July 17, 2019
• Study Completion (Actual): July 17, 2019

Study Registration Dates

• First Submitted: November 24, 2017
• First Submitted That Met QC Criteria: November 30, 2017
• First Posted (Actual): December 2, 2017

Study Record Updates

• Last Update Posted (Actual): February 21, 2021
• Last Update Submitted That Met QC Criteria: February 2, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hypoglycemia; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Sitagliptin Phosphate
• Other Study ID Numbers: DPP4-Hypo

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No